Study finds that blood test can gauge prostate cancer risk

January 16, 2008

By Flinn Foundation

[Source: TGen] – New genomics research has found that a simple blood test can determine which men are likely to develop prostate cancer. Researchers at the Translational Genomics Research Institute (TGen), Wake Forest University, the Karolinska Institutet in Stockholm, Sweden, and the Johns Hopkins Medical Institutions, found that five genetic variants previously associated with prostate cancer risk have a strong cumulative effect.

Published today in the “Online First” section of the New England Journal of Medicine, and in the February 28 print issue, researchers found that a man with four of the five variants has an increased risk of 400 to 500 percent compared to men with none of the variants. The researchers then added a family history of prostate cancer to the equation – for a total of six risk factors. A man with at least five of the six factors had increased risk of more than 900 percent. “This is a finding that could significantly impact patient care,” said senior researcher Jianfeng Xu, M.D., Dr. PH., Professor of epidemiology and cancer biology at Wake Forest University and a consultant to TGen. “Because this information could help physicians to better assess prostate cancer risk, a screening test using these five variants maybe particularly useful in men with a family history of prostate cancer or those who have a marginally elevated prostate specific antigen (PSA).”

Currently, age, race and family history are the three factors associated with increased risk of prostate cancer. Family history is believed to account for about 10 percent of prostate cancer cases; researchers estimated that the five variants combined could account for about 40 percent of cases. The study is one of the first to illustrate how a combination of several genes can affect risk of disease. The study involved analyzing DNA samples from 2,893 men with prostate cancer and 1,781 healthy individuals of similar ages – all participants of a prostate cancer study in Sweden. “These data show that a cumulative risk factor approach is likely a more powerful way of assessing risk as compared to looking at single risk factors,” said Dr. John Carpten, Ph.D., Director of TGen’s Division of Integrated Cancer Genomics. “Once the model is validated and refined, it is our hope that it will eventually equip physicians with a tool to help them make more informed clinical decisions.”

Until last year, no specific genetic variants had been consistently identified as markers for prostate cancer risk. Then, advances in technology allowed researchers to take a more systematic approach to looking at the entire genome. Instead of solely studying genes that they suspected were related to disease susceptibility, they could study the entire genome and look for associations. Through these searches, several research teams identified five genetic locations associated with risk of developing prostate cancer: three on chromosome 8q24, one on chromosome 17q12 and one on 17q24.3.

Each variant alone was associated with moderate risk, but the effect wasn’t considered significant enough to justify testing individuals. The current study was the first to evaluate whether there is a cumulative effect from having multiple variants. “When we considered the variants together we discovered their potential for predicting individual risk,” said David Duggan, Ph.D., an Investigator in TGen’s Genetic Basis of Human Disease Division. “Because of the cumulative effects of these risk variants and family history, for the first time associations found through genome-wide screening appear to be useful in clinical practice.”

The researchers said further study is needed to determine how their findings of genetic testing may complement PSA (prostate-specific antigen) testing. The researchers found that the risk associated with the genetic variants is independent of PSA results. “This suggests that a subset of men deemed to have a low risk of prostate cancer based on their PSA levels may in fact be at significantly elevated risk due to inheriting one or more of the genetic variants,” said S. Lilly Zheng, M.D., Associate Professor of internal medicine at Wake Forest and the first author of the paper. Genetic testing of these five variants will soon be offered at a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory at Wake Forest University School of Medicine.For more information, visit the web site http://www.proactivegenomics.com/ or call 866-487-2344. Co-researchers include senior author Henrik Gronberg, M.D., Ph.D. Professor at the Karolinska Institutet in Stockholm, Sweden, and William B. Isaacs, Ph.D, Professor at Johns Hopkins Medical Institutions in Baltimore, MD.